Generic protocol for vaccine effectiveness post implementation of a reactive mass vaccination campaign with oral cholera vaccine

Transcription

1 Generic protocol for vaccine effectiveness post implementation of a reactive mass vaccination campaign with oral cholera vaccine Version 18/12/2013 1

2 Table of Contents 1. Background Rationale Objectives Overall Objective Specific Objective Methods Study Definitions Case control study of an indicator group Surveillance, detection, interview of cases Laboratory procedures Identification interview of controls Statistical considerations Ethical considerations Timeline Annexes... 9 Annex 1: INFORMED CONSENT FORM:... 9 Annex 2: QUESTIONNAIRES FOR CHOLERA CASE-CONTROL STUDY

3 1. Background Cholera is an infection of the intestines caused by the bacterium vibrio cholerae. The infection is usually transmitted by consumption of contaminated food or water. In many cases, it can lead to severe watery diarrhea, dehydration in extreme cases, death. Two safe effective oral vaccines are currently recommended by the World Health Organization to reduce the risk of outbreaks of the disease in vulnerable populations, or can also serve to limit the spread of an existing outbreak. Consequently, mass vaccination campaigns will likely be carried out in many places where cholera is a risk. Vaccination campaigns can take place to prevent or quickly stop large outbreaks. Additional background on cholera vaccines can be found in the World Health Organization website. Many factors influence the degree of protection offered by vaccines. Therefore, in addition to estimating the proportion of the population who were vaccinated (i.e. vaccination coverage), it is also important to determine how well protected they are. Biological tests can provide some of this information, but monitoring rates of infection in a vaccinated population provide a more complete picture. Understing vaccine effectiveness helps to determine the actual risk cholera poses to a population at risk helps health authorities better plan health activities. 2. Rationale There is a need to identify effective strategies to prevent or quickly stop large cholera epidemics. The use of oral cholera vaccines in high-risk populations may offer one such solution. In combination with other studies, such as vaccine coverage, this protocol enables the assessment of whether the reactive cholera vaccine intervention in a selected, high-risk area is an effective strategy to reduce the consequences of cholera outbreaks. 3. Objectives 3.1 Overall Objective To evaluate the effectiveness of a mass vaccination campaign using oral cholera vaccine. The overall objective will be accomplished through achieving the following specific objectives 3.2 Specific Objective Assess vaccine effectiveness through a case control study of cholera infection following a mass vaccination campaign Assess the presence of selection bias related with health seeking behavior through a case control study of an indicator group 3

4 4. Methods 4.1 Study Definitions Date1 will be defined as the date at which the cholera mass vaccination campaign started for a defined catchment area. Date2 will be defined as the last day of the mass vaccination campaign. Date3 will be defined as the official end of the cholera season, as defined by the respective Ministry of Health, or in its absence, based on expert advice epidemiological evidence. A Cholera Treatment Center (CTC) will be defined as a health center set up or otherwise adapted for treating cholera cases in a defined catchment area. A Suspected Case will be defined as an individual who present to the CTC for treatment of acute watery diarrhea - whose onset of diarrhea was any time from date1 to the end of the cholera season - who present to the CTC for diarrhea for the first time since date1 - who are residents of the target area of the vaccination campaign since date1 - who were eligible for vaccination (i.e. not pregnant or under 2 years of age from date1 to date2. A Confirmed Case will be defined as a probably case with stool culture results positive for V. cholerae. Controls will be defined as individuals - who did not present the CTC for treatment of diarrhea - who would have sought care at the CTC for treatment of severe diarrhea from date1 - who were residents of the target vaccinated area since date1. - who were eligible for the vaccine (i.e. not pregnant or under 2 years of age from date1 to date2). 4.2 Case control study of an indicator group Additionally, an indicator group case-control study will be carried out to help rule out potential biases resulting from differential health seeking behavior between vaccinated unvaccinated individuals. The assumption is that similar vaccination status among cases controls would imply absence of significant health seeking behavior bias. 4

5 For the indicator case-control study, cases will be defined as individuals who present for treatment of acute watery diarrhea to the CTC but confirmed as not cholera diarrhea cases. Ideally, the indicator case control study should be started at least four months after vaccination (date3) if the rbs-wc vaccine is used considering the short-term protection offered by this vaccine against Escherichia coli. Cases will include only individuals: - whose onset of diarrhea was any time starting from date3 - who present to the CTC for diarrhea for the first time since date3 - who are residents of the target vaccinated area since date1 - who were eligible for vaccination (i.e. not pregnant or under 2 years of age from date1 to date2) - who are fecal sample negative for V. cholerae. Controls will consist of individuals: - who did not seek treatment for diarrhea at the CTC with symptoms starting from date3 to the focal time for the matched case - who are residents of the target vaccinated area since date1 - who were eligible for vaccination (i.e. not pregnant or under 2 years of age from date1 to date2) - who would have sought treatment at the CTC if they had developed severe watery diarrhea. 4.3 Surveillance, detection, interview of cases For both the primary case-control study indicator group case-control study, surveillance detection of potential cases will be done at the CTC. Individuals coming from the target vaccinated area of the selected locale will be identified at the CTC triage area. A log book will be maintained to list cases. Once the initial assessment rehydration is completed, each case will be requested to participate in the study. Informed consent will be obtained (see Annex 1). A stool sample will be collected for rapid testing from all individuals with diarrhea coming from the target vaccinated area of the defined locale. The eligibility criteria will be applied (i.e. check that the answer is no to all the screening questions in the questionnaire), then the questionnaire will be completed (see Annex 2). Information about 5

6 oral cholera vaccination details from the vaccination card will be collected only at the end of the interview. Completed questionnaires will be computerized in real time. 4.4 Laboratory procedures A dipstick test for vibrio cholerae O1 developed by the Institute Pasteur will be performed on a stool sample (200 μl) from individuals presenting to the CTC from the target vaccinated area in selected locale. The appearance of two pink lines (upper control line lower LPS positive line) indicates a positive result, a single upper pink control line indicates a negative result. For those patients with a positive result to the RDT, a filter paper disc will be dipped into fresh stool placed into a microtube with 2 to 3 drops of normal saline solution (NaCl 0.9%). The tubes will be kept at room temperature sent to the lab for isolation of V. cholerae according to stard methods 1. PCR can be also performed on the specimens sent to confirm the presence of V. cholerae 4.5 Identification interview of controls For both studies, four individually matched neighborhood controls will be recruited per case. Matching will be based on sex age range (0 to 1, 2 to 4, 5 to 14, or 15 years above) reside in the same township as the respective case. Controls will be selected through a walk around procedure starting from every third house to the right of the case s house (right h side while facing the house). An assembly log for controls will be maintained. This log will be an ordered list of all agesex- eligible with their names; addresses; whether they were found; if found, whether they agreed;, if they agreed, whether they were otherwise eligible. This log will have the information needed to go back to vaccination logs for both participating nonparticipating potential controls, to check for biased selection. For each control, after informed consent is obtained the eligibility criteria applied, the questionnaire will be completed (see Annex 2). Information about oral cholera vaccination details from the vaccination card will be collected only at the end of the interview. The completed questionnaires will be computerized in real time. 4.6 Statistical considerations - Endpoints: The odds (OR) of having been fully vaccinated (2 complete doses) will be compared with the odds of not being vaccinated between the cases controls through the odds ratio. 1 Dodin JFA. Diagnosis of the cholera vibrio. In: Paris IP, editor. Laboratory methods for the diagnosis of cholera vibrio other vibrios. Paris: p

7 - Sample size calculation: Using the following assumptions: tailed p value, 0.2 Beta error, 80% coverage a conservative estimate of 50% protective effect, 90 cases 360 controls would be necessary. A similar sample size will be needed for the indicator casecontrol study. - Ascertainment definition of vaccination: Vaccination status will be ascertained through information collected during the interview (recall from vaccination cards) from the computerized vaccination logs. The categories for documentation of vaccination for cases controls will be as follows. - written documentation of vaccination in vaccination card, vaccination log, or both; - vaccination by recall only as orally reported by the participant; - written documentation of non-vaccination in vaccination card, vaccination log, or both; - no vaccination by recall as orally reported by the participant; - unknown vaccination status by recall as orally reported by the participant The definition of fully vaccinated for the primary analysis of the cases controls is: written documentation in the vaccination log of intake of most or all of two doses of vaccine. - Analysis Plan The odds ratio for vaccination with two completely (or nearly completely) swallowed doses, separated by at least 10 days, with the second dose having been received at least 14 days before focal time (focal time is the date of onset of diarrhea for the cases) will be compared between the cases controls. Confounding variables will be adjusted by using conditional logistic regression models. The vaccine effectiveness (VE) equation can be expressed in the form of relative risk (RR), which in a case control study can be approximated by the OR. The VE will be calculated as follows: VE (%) = ( 1 OR) x 100 All p -values 95% confidence intervals will be two-sided. Statistical significance will be determined as a p -value less than Data will be analyzed using appropriate statistical analysis packages (e.g. STATA, SAS, SPSS, etc) 4.7 Ethical considerations This study will adhere to the principles that govern biomedical research involving human subjects as delineated in The Declaration of Helsinki 2 in order to provide assurance that the rights, integrity, confidentiality of trial subjects are protected. 2 World Medical Association. 7

8 Information about cholera, the vaccine, the study will be provided at community level, just prior to the first round of vaccination during the campaign. Written informed consent will be obtained from the participants or their parents / guardians prior to inclusion in the study (Annex 1). The privacy confidentiality of participants will be protected during following data collection. Before initiating of the study, the final protocol the written consent form will be submitted for clearance approval to the medical Ethics Review Committee of the Country. There are no direct benefits for participation in the case control study to determine vaccine effectiveness. The results of this study however will benefit all populations at risk of cholera infection by improving understing of the protection offered by vaccination. There are no anticipated risks for participation in the vaccine efficacy study. 4.8 Timeline - Each of two case-control studies is estimated to take 44 days to complete Preparation training: 14 days Field data collection: 30 days 8

9 5. Annexes Annex 1: INFORMED CONSENT FORM: I (or my child/ward) have been invited to take part in the research on cholera. I have read the information letter concerning the study, or it has been read to me. I have had the opportunity to ask questions about it any questions that I have asked have been answered to my satisfaction. I consent voluntarily to participate (or for my child/ward to participate) as a subject in this study underst that I have the right to withdraw from the study at any time without in any way affecting my (or my child/ward s) medical care. Print Name of Subject Date Signature of Subject / / (dd/mm/yy) If illiterate Print Name of Independent Literate Witness Date Signature of Witness (if possible, this person should be selected by the participant should have no connection to the research team) / / (dd/mm/yy) Print Name of Researcher Date Signature of Researcher / / (dd/mm/yy) 9

10 Annex 2: QUESTIONNAIRES FOR CHOLERA CASE-CONTROL STUDY A. QUESTIONNAIRE FOR INDIVIDUALS PRESENTING TO THE CTC WITH DIARRHOEA STARTING AFTER THE VACCINATION CAMPAIGN Screening questions: Include only cases from the target area if he/she answers no to ALL the following questions. Did this diarrhea episode start before date1 (starting day of the vaccination campaign)? Did he/she seek treatment for diarrhea at the CTC anytime from date1 but BEFORE this current episode? Was he/she living in a place other than the target area from date1 to the present? If female, was she pregnant from date1 to the date2 (end of the campaign)? If child, was he/she under 2 years of age from date1 to date2? A: IDENTIFICATION A1 Name A2 Age... A3 Sex F[ ] M[ ] A4 How many people are living in your household? 1 to 5 1 [ ] 6 to 14 2[ ] More than 15 3 [ ] B: RESIDENCE DURING THE LAST WEEK URBAN ZONE: B1 City... B2 Constituency..... B3 Township..... B4 Street... B5 No... B6 Other references RURAL ZONE B7Province... B8 Constituency B9 Village..... B10 Street......B11 No... B12 Other references B14 GPS COORDINATES: S... E... Nom... C: SYMPTOMS C1 Diarrhea: No 2 [ ] Yes 1 [ ] Date of onset.../.../... C2 Frequency: times/day... 10

11 C3 Type:... C4 Vomiting: No 2 [ ] Yes 1 [ ] Date of onset.../.../... C5 Dehydration: No 2 [ ] Yes 1 [ ] C6 ADMISSION TO THE CTC Date.../.../... C7 STOOL SAMPLE Date of collection.../.../... C8 Did you take: Antibiotics: No 2 [ ] Yes 1 [ ] If yes, date.../.../... Specify:... C9: CLINICAL DIAGNOSIS: CHOLERA [ ] SIMPLE DIARRHOEA [ ] OTHER [ ] SPECIFY... D: HISTORY OF CHOLERA & HOUSEHOLD CONTACTS) D1 VISITORS LIVING IN YOUR HOUSE DURING THE PAST 5 DAYS Name... where now?... Name... where now?... Name... where now?... D2 Did you ever have cholera during the previous years? No 2 [ ] Yes 1 [ ] If yes, when... D3 Did any member of your family have cholera during the previous years? No 2 [ ] Yes 1 [ ] D4 If yes, how many? < 5 1 [ ] 5 a 14 2 [ ] 15 or more 3 [ ] when... Other cases of diarrhea during the last week: D5 Family members: No 2 [ ] Yes 1 [ ] D6 Neighbors or friends: No 2 [ ] Yes 1 [ ] Don t know 3 [ ] E: WATER SUPPLY E1 Normally, what is your usual source for drinking water? Piped into the house 1 [ ] St pipe/public tap 2 [ ] Individual well 3 [ ] Community well 4 [ ] Purchased 5 [ ] Collected directly from a lake or other source 6 [ ] Other 7 [ ]... E2 During the last five days, what was the source of your drinking water? E3 Approximately how many persons utilize the same water source? 1 1 [ ] [ ] [ ] [ ] > [ ] E4 Describe your water source: Concrete well with pump 1 [ ] Concrete well manual, covered 2 [ ] 11

12 Concrete well - open 3 [ ] Well without concrete - open 4 [ ] Piped 5 [ ] E5 Is the water from the source visibly contaminated? No 2 [ ] Yes 1 [ ] No Obs 3 [ ] E6 GPS Coordinates: S... Nom... E7 MAIN SOURCE: Chlorine more than 0.3 MG/L No 2 [ ] Yes 1 [ ] E8 HOUSE WATER: Chlorine more than 0.3 MG/L No 2 [ ] Yes 1 [ ] E9 Do you treat your water now?... F: WATER STORAGE AND TREATMENT F1 What type of container do you use for storing your DRINKING WATER? Plastic bucket 1 [ ] Metal bucket 2 [ ] Clay pot 3 [ ] Tank or cistern 4 [ ] Motor oil container 5 [ ] Metallic pot 6 [ ] 200-litre metal container 7 [ ] 20-litre bottle 8 [ ] Other 9 [ ]... F2 During the last 5 days, how do you ensure that your water is safe for drinking? Boil 1 [ ] Cover 2 [ ] Filter 3 [ ] Treat with chlorine 4 [ ] Use other chemicals 5 [ ] No answer 6 [ ] Other 7 [ ]... G: FOOD CONSUMED DURING THE PAST 5 DAYS G1 Type of uncooked food:... G2 Milk products: No 2 [ ] Yes 1 [ ] What... G3 Fresh fish: No 2 [ ] Yes 1 [ ] What... G4 Dried fish: No 2 [ ] Yes 1 [ ] What... G5 Fresh seafood: No 2 [ ] Yes 1 [ ] What... G6 Dried seafood: No 2 [ ] Yes 1 [ ] What... G7 Did you eat cooked food from the market? No 2 [ ] Yes 1 [ ] If yes, what kind?... G8 Where did you eat during the last 5 days? Residence 2 [ ] Outside your residence 1 [ ] If outside, where?... H: TOILET H 1 Do you have a toilet in your house? None 2 [ ] Yes 1 [ ] 12

13 He Normally, where do you defecate? No mato 1 [ ] Toilet inside the house 2 [ ] Communal toilet 3 [ ] Individual latrine (covered with concrete) 4 [ ] Simple latrine (no cement) 5 [ ] Communal latrine (with cement) 6 [ ] Anywhere 7 [ ] Other 8 [ ]... J: SOCIO-ECONOMIC STATUS J1 How many animals does your household have? Goats 1 [ ] Pigs 2 [ ] Ducks 3 [ ] Chickens 4 [ ] Other 5 [ ] (Specify)... J2 How many of these does your household have: Bicycles [ ] Radios [ ] Metal pots[ ] Woking watches/clocks [ ] Electricity in the house[ ] Cars[ ] Television[ ] Cellular phone [ ] Mosquito nets [ ] Soap [ ] J3 Do you have a field for planting? No[ ] Yes[ ] J4 Other than working in the field, how many members of your family have sources of income? [ ] J5 Who is the main source of household income? What is this household member s job? Fisherman 1 [ ] Selling goats along the road 2 [ ] Farmer 3 [ ] Small scale farmer 4 [ ] Laborer 5 [ ] Other service worker 6 [ ] Technician 8 [ ]. Professional 8 [ ]... Other 9 [ ] (specify.). J6 Is there anybody sick in the household?... J7 Do you know to write read?... K: LABORATORY RESULTS K1 Negative 2 [ ] Positive 1 [ ] Date.../.../... Antibiotic susceptibility... K3 HEALTH UNIT... K4 Date of data collection.../.../... Other important comments: By observation: Toilet in the house No 2 [ ] Yes 1 [ ] Don t know 3 [ ] L. Did he/she come directly to the CTC to seek treatment for this episode of diarrhea? No [ ] Yes [ ] If no, list (in order) where he/she sought treatment prior to coming to the CTC:.. M. RESULT OF RAPID TEST L1 Negative 2 [ ] Positive 1 [ ] Data.../.../... N. CHOLERA VACCINATION 13

14 Did you receive the cholera vaccine given in date1 date2? No 2 [ ] Yes 1 [ ] Don t know 3 [ ] If yes, how many doses? Two 2 [ ] One 1 [ ] Don t know 3 [ ] If his/her vaccination card is available, copy the following information from the card. Vaccination card serial number: Received dose 1? No 2 [ ] Yes 1 [ ] Was dose 1 ingested? Incompletely 2 [ ] Completely 1 [ ] Received dose 2? No 2 [ ] Yes 1 [ ] Was dose 2 ingested? Incompletely 2 [ ] Completely 1 [ ] 14

15 B. QUESTIONNAIRE FOR CONTROLS Screening questions: Include only controls from the target area if he/she answers no to ALL the following questions. Did he/she seek treatment at the CTC for diarrhea which started from date /------/ (date of onset of diarrhea of the case)? Was he/she living in a place other than the target area date1 to the present? If female, was she pregnant from date1 to date2? If child, was he/she under 2 years of age from date1 to date2? In case he/she develops severe watery diarrhea, would he/she go to a treatment facility other than the CTC? A: IDENTIFICATION A1 Name A2 Age... A3 Sex F[ ] M[ ] A4 How many people are living in your household? 1 to 5 1 [ ] 6 to 14 2[ ] More than 15 3 [ ] B: RESIDENCE DURING THE LAST WEEK URBAN ZONE: B1 City... B2 Constituency..... B3 Township..... B4 Street... B5 No... B6 Other references RURAL ZONE B7Province... B8 Constituency B9 Village..... B10 Street......B11 No... B12 Other references B14 GPS COORDINATES: S... E... Nom... D: HISTORY OF CHOLERA & HOUSEHOLD CONTACTS) D1 VISITORS LIVING IN YOUR HOUSE DURING THE PAST 5 DAYS 15

16 Name... where now?... Name... where now?... Name... where now?... D2 Did you ever have cholera during the previous years? No 2 [ ] Yes 1 [ ] If yes, when... D3 Did any member of your family have cholera during the previous years? No 2 [ ] Yes 1 [ ] D4 If yes, how many? < 5 1 [ ] 5 a 14 2 [ ] 15 or more 3 [ ] when... Other cases of diarrhea during the last week: D5 Family members: No 2 [ ] Yes 1 [ ] D6 Neighbors or friends: No 2 [ ] Yes 1 [ ] Don t know 3 [ ] E: WATER SUPPLY E1 Normally, what is your usual source for drinking water? Piped into the house 1 [ ] St pipe/public tap 2 [ ] Individual well 3 [ ] Community well 4 [ ] Purchased 5 [ ] Collected directly from a lake or other source 6 [ ] Other 7 [ ]... E2 During the last five days, what was the source of your drinking water? E3 Approximately how many persons utilise the same water source? 1 1 [ ] [ ] [ ] [ ] > [ ] E4 Describe your water source: Concrete well with pump 1 [ ] Concrete well manual, covered 2 [ ] Concrete well - open 3 [ ] Well without concrete - open 4 [ ] Piped 5 [ ] E5 Is the water from the source visibly contaminated? No 2 [ ] Yes 1 [ ] No Obs 3 [ ] E6 GPS Coordinates: S... Nom... E7 MAIN SOURCE: Chlorine more than 0.3 MG/L No 2 [ ] Yes 1 [ ] E8 HOUSE WATER: Chlorine more than 0.3 MG/L No 2 [ ] Yes 1 [ ] E9 Do you treat your water now?... F: WATER STORAGE AND TREATMENT F1 What type of container do you use for storing your DRINKING WATER? Plastic bucket 1 [ ] Metal bucket 2 [ ] Clay pot 3 [ ] Tank or cistern 4 [ ] 16

17 Motor oil container 5 [ ] Metallic pot 6 [ ] 200-litre metal container 7 [ ] 20-litre bottle 8 [ ] Other 9 [ ]... F2 During the last 5 days, how do you ensure that your water is safe for drinking? Boil 1 [ ] Cover 2 [ ] Filter 3 [ ] Treat with chlorine 4 [ ] Use other chemicals 5 [ ] No answer 6 [ ] Other 7 [ ]... G: FOOD CONSUMED DURING THE PAST 5 DAYS G1 Type of uncooked food:... G2 Milk products: No 2 [ ] Yes 1 [ ] What... G3 Fresh fish: No 2 [ ] Yes 1 [ ] What... G4 Dried fish: No 2 [ ] Yes 1 [ ] What... G5 Fresh seafood: No 2 [ ] Yes 1 [ ] What... G6 Dried seafood: No 2 [ ] Yes 1 [ ] What... G7 Did you eat cooked food from the market? No 2 [ ] Yes 1 [ ] If yes, what kind?... G8 Where did you eat during the last 5 days? Residence 2 [ ] Outside your residence 1 [ ] If outside, where?... H: TOILET H 1 Do you have a toilet in your house? None 2 [ ] Yes 1 [ ] He Normally, where do you defecate? No mato 1 [ ] Toilet inside the house 2 [ ] Communal toilet 3 [ ] Individual latrine (covered with concrete) 4 [ ] In the sea 5 [ ] Simple latrine (no cement) 6 [ ] Communal latrine (with cement) 7 [ ] Anywhere 8 [ ] Other 9 [ ]... J: SOCIO-ECONOMIC STATUS J1 How many animals does your household have? Goats 1 [ ] Pigs 2 [ ] Ducks 3 [ ] Chickens 4 [ ] Other 5 [ ] (Specify)... J2 How many of these does your household have: Bicycles [ ] Radios [ ] Metal pots[ ] Woking watches/clocks [ ] Electricity in the house[ ] Cars[ ] Television[ ] Cellular phone [ ] Mosquito nets [ ] Soap [ ] J3 Do you have a field for planting? No[ ] Yes[ ] 17

18 J4 Other than working in the field, how many members of your family have sources of income? [ ] J5 Who is the main source of household income? What is this household member s job? Fisherman 1 [ ] Selling goats along the road 2 [ ] Farmer 3 [ ] Small scale farmer 4 [ ] Labourer 5 [ ] Other service worker 6 [ ] Technician 8 [ ]. Professional 8 [ ]... Other 9 [ ] (specify.). J6 Is there anybody sick in the household?... J7 Do you know to write read?... K. HEALTH UTILIZATION BEHAVIOR FOR DIARRHOEA When you have SEVERE diarrhea what do you do to treat it? Go to a health unit 1 [ ] specify..... Take ORS 2 [ ] Go to the pharmacy 3 [ ] Consult a traditional healer 4 [ ] Other 4 [ ] specify... L. CHOLERA VACCINATION Did you receive the cholera vaccine given in (vaccination dates)? No 2 [ ] Yes 1 [ ] Don t know 3 [ ] If yes, how many doses? Two 2 [ ] One 1 [ ] Don t know 3 [ ] If his/her vaccination card is available, copy the following information from the card. Vaccination card serial number: Received dose 1? No 2 [ ] Yes 1 [ ] Was dose 1 ingested? Incompletely 2 [ ] Completely 1 [ ] Received dose 2? No 2 [ ] Yes 1 [ ] Was dose 2 ingested? Incompletely 2 [ ] Completely 1 [ ] 18